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Published in: Journal of Translational Medicine 1/2013

Open Access 01-12-2013 | Research

Flotillin-2 is associated with breast cancer progression and poor survival outcomes

Authors: Xi Wang, Qi Yang, Ling Guo, Xing-Hua Li, Xiao-Hui Zhao, Li-Bing Song, Huan-Xin Lin

Published in: Journal of Translational Medicine | Issue 1/2013

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Abstract

Background

Flotillin-2 (FLOT2) has been implicated in several signaling pathways in tumor cells. Our study aimed to investigate the expression pattern and clinicopathological significance of FLOT2 in patients with breast cancer.

Methods

The expression level of FLOT2 in normal breast epithelial cells, breast cancer cell lines, and four breast cancer biopsies paired with adjacent noncancerous tissues were quantified using real-time RT-PCR and Western blotting. FLOT2 protein expression was analyzed in 171 archived paraffin-embedded breast cancer samples using immunohistochemistry (IHC). Statistical analyses were performed to evaluate the clinicopathological significance of FLOT2 expression.

Results

FLOT2 was significantly upregulated in breast cancer cell lines and tissue samples compared with normal cells and adjacent noncancerous breast tissues, respectively. IHC analysis revealed high expression levels of FLOT2 in 82 of 171 (48.0%) breast cancer specimens. Statistical analysis revealed that FLOT2 expression was significantly correlated with clinical stage (P < 0.001), T classification (P < 0.001), M classification (P < 0.001), histological differentiation (P = 0.005) and ErbB2 expression (P = 0.003). Patients with higher levels of FLOT2 expression had a shorter overall survival duration than patients with lower FLOT2 expression levels. Multivariate analysis suggested that FLOT2 expression was an independent prognostic marker for survival in patients with breast cancer.

Conclusions

The current results demonstrated that high FLOT2 protein expression was associated with poor outcomes in patients with breast cancer. FLOT2 could be used as a prognostic biomarker for breast cancer progression.
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Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed
2.
go back to reference Robbins P, Pinder S, De Klerk N, Dawkins H, Harvey J, Sterrett G, Ellis I, Elston C: Histological grading of breast carcinomas: a study of interobserver agreement. Hum Pathol. 1995, 26: 873-879. 10.1016/0046-8177(95)90010-1.CrossRefPubMed Robbins P, Pinder S, De Klerk N, Dawkins H, Harvey J, Sterrett G, Ellis I, Elston C: Histological grading of breast carcinomas: a study of interobserver agreement. Hum Pathol. 1995, 26: 873-879. 10.1016/0046-8177(95)90010-1.CrossRefPubMed
3.
go back to reference Elston CW, Ellis IO: Pathological prognostic factors in breast cancer I: the value of histological gradeinbreast cancer: experience from a large study with long-term follow-up. Histopathology. 1991, 19: 403-410. 10.1111/j.1365-2559.1991.tb00229.x.CrossRefPubMed Elston CW, Ellis IO: Pathological prognostic factors in breast cancer I: the value of histological gradeinbreast cancer: experience from a large study with long-term follow-up. Histopathology. 1991, 19: 403-410. 10.1111/j.1365-2559.1991.tb00229.x.CrossRefPubMed
4.
go back to reference Galea MH, Blamey RW, Elston CE, Ellis IO: The Nottingham prognostic index in primary breast cancer. Breast Cancer Res Treat. 1992, 22: 207-219. 10.1007/BF01840834.CrossRefPubMed Galea MH, Blamey RW, Elston CE, Ellis IO: The Nottingham prognostic index in primary breast cancer. Breast Cancer Res Treat. 1992, 22: 207-219. 10.1007/BF01840834.CrossRefPubMed
5.
go back to reference Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O’Malley F, Simpson JF, Connolly JL, Hayes DF, Edge SB, Lichter A, Schnitt SJ: Prognostic factors in breast cancer: College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000, 124: 966-978.PubMed Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O’Malley F, Simpson JF, Connolly JL, Hayes DF, Edge SB, Lichter A, Schnitt SJ: Prognostic factors in breast cancer: College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000, 124: 966-978.PubMed
6.
go back to reference Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed
7.
go back to reference Schulte T, Paschke KA, Laessing U, Lottspeich F, Stuermer CA: Reggie-1 and reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration. Development. 1997, 124: 577-587.PubMed Schulte T, Paschke KA, Laessing U, Lottspeich F, Stuermer CA: Reggie-1 and reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration. Development. 1997, 124: 577-587.PubMed
8.
go back to reference Lang DM, Lommel S, Jung M, Ankerhold R, Petrausch B, Laessing U, Wiechers MF, Plattner H, Stuermer CA: Identification of reggie-1 and reggie-2 as plasmamembrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons. J Neurobiol. 1998, 37: 502-523. 10.1002/(SICI)1097-4695(199812)37:4<502::AID-NEU2>3.0.CO;2-S.CrossRefPubMed Lang DM, Lommel S, Jung M, Ankerhold R, Petrausch B, Laessing U, Wiechers MF, Plattner H, Stuermer CA: Identification of reggie-1 and reggie-2 as plasmamembrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons. J Neurobiol. 1998, 37: 502-523. 10.1002/(SICI)1097-4695(199812)37:4<502::AID-NEU2>3.0.CO;2-S.CrossRefPubMed
9.
go back to reference Munro S: Lipid rafts: elusive or illusive?. Cell. 2003, 115: 377-388. 10.1016/S0092-8674(03)00882-1.CrossRefPubMed Munro S: Lipid rafts: elusive or illusive?. Cell. 2003, 115: 377-388. 10.1016/S0092-8674(03)00882-1.CrossRefPubMed
10.
go back to reference Carver LA, Schnitzer JE, Anderson RG, Mohla S: Role of caveolae and lipid rafts in cancer: workshop summary and future needs. Cancer Res. 2003, 63: 6571-6574.PubMed Carver LA, Schnitzer JE, Anderson RG, Mohla S: Role of caveolae and lipid rafts in cancer: workshop summary and future needs. Cancer Res. 2003, 63: 6571-6574.PubMed
11.
go back to reference Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000, 1: 31-39. 10.1038/35036052.CrossRefPubMed Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000, 1: 31-39. 10.1038/35036052.CrossRefPubMed
12.
go back to reference Hazarika P, McCarty MF, Prieto VG, George S, Babu D, Koul D, Bar-Eli M, Duvic M: Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res. 2004, 64: 7361-7369. 10.1158/0008-5472.CAN-04-0823.CrossRefPubMed Hazarika P, McCarty MF, Prieto VG, George S, Babu D, Koul D, Bar-Eli M, Duvic M: Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res. 2004, 64: 7361-7369. 10.1158/0008-5472.CAN-04-0823.CrossRefPubMed
13.
go back to reference Rickman DS, Millon R, De Reynies A, Thomas E, Wasylyk C, Muller D, Abecassis J, Wasylyk B: Prediction of future metastasis and molecular characterization of head and neck squamous-cell carcinoma based on transcriptome and genome analysis by microarrays. Oncogene. 2008, 27: 6607-6622. 10.1038/onc.2008.251.CrossRefPubMed Rickman DS, Millon R, De Reynies A, Thomas E, Wasylyk C, Muller D, Abecassis J, Wasylyk B: Prediction of future metastasis and molecular characterization of head and neck squamous-cell carcinoma based on transcriptome and genome analysis by microarrays. Oncogene. 2008, 27: 6607-6622. 10.1038/onc.2008.251.CrossRefPubMed
14.
go back to reference Pust S, Klokk TI, Musa N, Jenstad M, Risberg B, Erikstein B, Tcatchoff L, Liestøl K, Danielsen HE, Van Deurs B, Sandvig K: Flotillins as regulators of ErbB2 levels in breast cancer. Oncogene. 2013, 32: 3443-3451. 10.1038/onc.2012.357.CrossRefPubMed Pust S, Klokk TI, Musa N, Jenstad M, Risberg B, Erikstein B, Tcatchoff L, Liestøl K, Danielsen HE, Van Deurs B, Sandvig K: Flotillins as regulators of ErbB2 levels in breast cancer. Oncogene. 2013, 32: 3443-3451. 10.1038/onc.2012.357.CrossRefPubMed
15.
go back to reference Berger T, Ueda T, Arpaia E, Chio II, Shirdel EA, Jurisica I, Hamada K, You-Ten A, Haight J, Wakeham A, Cheung CC, Mak TW: Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model. Oncogene. in press Berger T, Ueda T, Arpaia E, Chio II, Shirdel EA, Jurisica I, Hamada K, You-Ten A, Haight J, Wakeham A, Cheung CC, Mak TW: Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model. Oncogene. in press
16.
go back to reference Li J, Zhang N, Song LB, Liao WT, Jiang LL, Gong LY, Wu J, Yuan J, Zhang HZ, Zeng MS, Li M: Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Clin Cancer Res. 2008, 14: 3319-3326. 10.1158/1078-0432.CCR-07-4054.CrossRefPubMed Li J, Zhang N, Song LB, Liao WT, Jiang LL, Gong LY, Wu J, Yuan J, Zhang HZ, Zeng MS, Li M: Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Clin Cancer Res. 2008, 14: 3319-3326. 10.1158/1078-0432.CCR-07-4054.CrossRefPubMed
17.
go back to reference Satyamoorthy K, Li G, Gerrero MR, Brose MS, Volpe P, Weber BL, Van Belle P, Elder DE, Herlyn M: Constitutive mitogen activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res. 2003, 63: 756-759.PubMed Satyamoorthy K, Li G, Gerrero MR, Brose MS, Volpe P, Weber BL, Van Belle P, Elder DE, Herlyn M: Constitutive mitogen activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res. 2003, 63: 756-759.PubMed
18.
go back to reference McAuliffe PF, Meric-Bernstam F, Mills GB, Gonzalez-Angulo AM: Deciphering the role of PI3K/Akt/mTOR pathway in breast cancer biology and pathogenesis. Clin Breast Cancer. 2010, 10 (Suppl 3): 59-65.CrossRef McAuliffe PF, Meric-Bernstam F, Mills GB, Gonzalez-Angulo AM: Deciphering the role of PI3K/Akt/mTOR pathway in breast cancer biology and pathogenesis. Clin Breast Cancer. 2010, 10 (Suppl 3): 59-65.CrossRef
Metadata
Title
Flotillin-2 is associated with breast cancer progression and poor survival outcomes
Authors
Xi Wang
Qi Yang
Ling Guo
Xing-Hua Li
Xiao-Hui Zhao
Li-Bing Song
Huan-Xin Lin
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2013
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-11-190

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